Stevens-Johnson综合征(SJS)和中毒性表皮坏死松解症(TEN)较少见,目前没有任何控制良好的临床试验或流行病学研究来确定确切的患病率和发病率。 据估计,所有种族、年龄和性别中,SJS的年发病率为每百万人1~6例,TEN的年发病率为每百万人0.4~1.2例。[10]Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600-1608.http://www.nejm.org/doi/full/10.1056/NEJM199512143332404#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/7477195?tool=bestpractice.com 一项病例对照研究显示,在引起 SJS 和 TEN 的药物中,磺胺类药物抗菌剂有较高的风险,每周每百万暴露人群中 4.5 例发病。[10]Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600-1608.http://www.nejm.org/doi/full/10.1056/NEJM199512143332404#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/7477195?tool=bestpractice.com 一些暴露于特定药物的群体,与不应用这些药物的人群相比,其发病率和患病率会增加,如癫痫患者服用抗惊厥药或HIV阳性患者应用抗HIV药物。 HIV阳性患者SJS和TEN的总发病率为每年每千人中1例。[11]Coopman SA, Johnson RA, Platt R, et al. Cutaneous disease and drug reactions in HIV infection. N Engl J Med. 1993;328:1670-1674.http://www.nejm.org/doi/full/10.1056/NEJM199306103282304#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/8487826?tool=bestpractice.com[12]Mittmann N, Knowles SR, Koo M, et al. Incidence of toxic epidermal necrolysis and Stevens-Johnson Syndrome in an HIV cohort: an observational, retrospective case series study. Am J Clin Dermatol. 2012;13:49-54.http://www.ncbi.nlm.nih.gov/pubmed/22145749?tool=bestpractice.com
一项综述显示,根据处方的数量或每天服用剂量估计,服用卡马西平,拉莫三嗪,苯巴比妥和苯妥英钠新患者发病的风险从万分之一到万分之十不等,低于丙戊酸。[13]Mockenhaupt M, Messenheimer J, Tennis P, et al. Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology. 2005;64:1134-1138.http://www.ncbi.nlm.nih.gov/pubmed/15824335?tool=bestpractice.com[14]Calabrese JR, Sullivan JR, Bowden CL, et al. Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. J Clin Psychiatry. 2002 Nov;63(11):1012-9.http://www.ncbi.nlm.nih.gov/pubmed/12444815?tool=bestpractice.com 其他危险因素有放疗,胶原血管病,移植和疱疹病毒感染。[10]Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600-1608.http://www.nejm.org/doi/full/10.1056/NEJM199512143332404#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/7477195?tool=bestpractice.com
药物基因组学研究表明种族和HLA分型可能导致药物不良反应。[15]Yip VL, Alfirevic A, Pirmohamed M. Genetics of immune-mediated adverse drug reactions: a comprehensive and clinical review. Clin Rev Allergy Immunol. 2015;48:165-175.http://www.ncbi.nlm.nih.gov/pubmed/24777842?tool=bestpractice.com[16]Chang CC, Too CL, Murad S, et al. Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population. Int J Dermatol. 2011;50:221-224.http://www.ncbi.nlm.nih.gov/pubmed/212244392?tool=bestpractice.com[17]Chung WH, Hung SI. Genetic markers and danger signals in stevens-johnson syndrome and toxic epidermal necrolysis. Allergol Int. 2010;59:325-332.http://www.ncbi.nlm.nih.gov/pubmed/20962567?tool=bestpractice.com[18]Leckband SG, Kelsoe JR, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther. 2013;94:324-328.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748365/http://www.ncbi.nlm.nih.gov/pubmed/23695185?tool=bestpractice.com[19]Ueta M, Sawai H, Sotozono C, et al. IKZF1, a new susceptibility gene for cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis with severe mucosal involvement. J Allergy Clin Immunol. 2015;135:1538-1545.http://www.ncbi.nlm.nih.gov/pubmed/25672763?tool=bestpractice.com 在中国汉族人,HLA-B*1502等位基因与卡马西平诱导的SJS和TEN强相关;在美国,FDA建议所有亚洲人在处方此药之前进行检测。[16]Chang CC, Too CL, Murad S, et al. Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population. Int J Dermatol. 2011;50:221-224.http://www.ncbi.nlm.nih.gov/pubmed/212244392?tool=bestpractice.com HLA-A*0206和HLA-B*4403与感冒药诱发的SJS和TEN相关。[19]Ueta M, Sawai H, Sotozono C, et al. IKZF1, a new susceptibility gene for cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis with severe mucosal involvement. J Allergy Clin Immunol. 2015;135:1538-1545.http://www.ncbi.nlm.nih.gov/pubmed/25672763?tool=bestpractice.com HLA-A*3101与伴眼部等并发症的SJS和TEN强相关,不分种族。[15]Yip VL, Alfirevic A, Pirmohamed M. Genetics of immune-mediated adverse drug reactions: a comprehensive and clinical review. Clin Rev Allergy Immunol. 2015;48:165-175.http://www.ncbi.nlm.nih.gov/pubmed/24777842?tool=bestpractice.com 。 所有携带HLA-B*5801的个体均存在别嘌呤醇诱发SJS/TEN的风险。[20]Hershfield MS, Callaghan JT, Tassaneeyakul W, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93:153-158.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564416/http://www.ncbi.nlm.nih.gov/pubmed/23232549?tool=bestpractice.com
出现 HLA-B*1502、HLA-C*0602 或 HLA-C*0801 等位基因与甲氧苄啶/磺胺甲噁唑诱导性 SJS/TEN 相关。[2]Dodiuk-Gad RP, Chung WH, Valeyrie-Allanore L, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: an update. Am J Clin Dermatol. 2015;16:475-493.http://www.ncbi.nlm.nih.gov/pubmed/26481651?tool=bestpractice.com[21]Kongpan T, Mahasirimongkol S, Konyoung P, et al. Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions. Pharmacogenet Genomics. 2015;25:402-411.http://www.ncbi.nlm.nih.gov/pubmed/26086150?tool=bestpractice.com 美国食品药品监督管理局 (US Food and Drug Administration) 建议在开始使用阿巴卡韦治疗 HIV 感染之前对患者进行 HLA-B*5701 等位基因筛查。[22]Tangamornsuksan W, Lohitnavy O, Kongkaew C, et al. Association of HLA-B*5701 genotypes and abacavir-induced hypersensitivity reaction: a systematic review and meta-analysis. J Pharm Pharm Sci. 2015;18:68-76.http://ejournals.library.ualberta.ca/index.php/JPPS/article/view/23356/18071http://www.ncbi.nlm.nih.gov/pubmed/25877443?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: 中毒性表皮坏死松解症伴表皮剥脱、眼部受累、坏疽性臁疮来自Dr A. Kowal-Vern个人收集 [Citation ends].